Transient spectroscopy has been used to study the photo-induced dissociation of carbon monoxide from hemoglobin. The data provide a detailed description of the pathway for ligand dissociation, revealing three distinct structural relaxations in the unliganded protein. Experiments on hybrid iron-cobalt hemoglobin show spectral changes in the cobalt hemes which can be used to determine how rapidly structural changes initiated by photolysis of CO from the Fe hemes are propagated to other subunits. Effort has been focussed on interpreting the spectral changes observed in these experiments. To compare spectral changes from molecules in which the ligand-rebinding kinetics to the Fe hemes are different, the rebinding curves must be known accurately. An improved analysis of ligand binding has been developed which permits us to compare spectral changes for the hybrids and normal hemoglobin and resolve the spectra changes from the Co subunits. When the delay time for polymerization of sickle cell hemoglobin exceeds 1 sec the kinetics of polymerization become stochastic when the reaction is monitored in very small volumes (less than 10 to the -10cc). The distribution of delay times can be measured by performing several hundred identical experiments. During the past year a simple theory has been developed which permits these distributions to be analyzed to give the homogeneous nucleation rate and other parameters of the dual-nucleation model proposed by Ferrone et al., (1980). Interpretation of these distribution permits us to evaluate the temperature dependence of the homogeneous nucleation rate and to obtain direct estimates of the size of the nucleus. The results supplement the analysis of bulk experiments using the same model which has been completed in collaboration with Dr. Ferrone. Together, these two studies show that this model provides an excellent description of the nucleation controlled polymerization of hemoglobin S.